Antioxidant Small Molecule Compound Chrysin Promotes the Self-Renewal of Hematopoietic Stem Cells
There is an increasing demand for the expansion of functional human hematopoietic stem cells (hHSCs) for various clinical applications. Based on our primary screening of antioxidant small molecule compounds library, a small molecule compound C2968 (chrysin) was identificated to expand cord blood CD3...
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Frontiers Media S.A.
2020-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00399/full |
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| author | Yinghui Li Mei He Wenshan Zhang Ming Yang Yahui Ding Shiqi Xu Jiali Gu Yafang Li Jingjing Yin Yingdai Gao |
| author_facet | Yinghui Li Mei He Wenshan Zhang Ming Yang Yahui Ding Shiqi Xu Jiali Gu Yafang Li Jingjing Yin Yingdai Gao |
| author_sort | Yinghui Li |
| collection | DOAJ |
| description | There is an increasing demand for the expansion of functional human hematopoietic stem cells (hHSCs) for various clinical applications. Based on our primary screening of antioxidant small molecule compounds library, a small molecule compound C2968 (chrysin) was identificated to expand cord blood CD34+ cells in vitro. Then we further verified the optimum concentration and explored its effect on hHSCs phenotype and biological function. C2968 could significantly increase the proportion and absolute number of CD34+CD38−CD49f+ and CD34+CD38−CD45RA−CD90+ cells under 2.5 μM. Furthermore, the total number of colony-forming units and the frequency of LT-HSCs in C2968-treated group were significantly higher than control, indicating the multipotency and long-term activity of hematopoietic stem and progenitor cells were sustained. Additionally, C2968 treatment could maintain transplantable HSCs that preserve balanced multilineage potential and promote rapid engraftment after transplantation in immunodeficient (NOG) mice. Mechanistically, the activity of chrysin might be mediated through multiple mechanisms namely delaying HSC differentiation, inhibiting ROS-activated apoptosis, and modulating of cyclin-dependent kinase inhibitors. Overall, chrysin showed good ex vivo expansion effect on hHSCs, which could maintain the self-renewal and multilineage differentiation potential of hHSCs. Through further research on its antioxidant mechanism, it may become a promising tool for further fundamental research and clinical umbilical cord blood transplantation of hHSCs. |
| first_indexed | 2024-12-10T14:20:20Z |
| format | Article |
| id | doaj.art-9ce283f8bc7d4084bf31cc3c5ddee13a |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-10T14:20:20Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-9ce283f8bc7d4084bf31cc3c5ddee13a2022-12-22T01:45:12ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-04-011110.3389/fphar.2020.00399518250Antioxidant Small Molecule Compound Chrysin Promotes the Self-Renewal of Hematopoietic Stem CellsYinghui Li0Mei He1Wenshan Zhang2Ming Yang3Yahui Ding4Shiqi Xu5Jiali Gu6Yafang Li7Jingjing Yin8Yingdai Gao9State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaThere is an increasing demand for the expansion of functional human hematopoietic stem cells (hHSCs) for various clinical applications. Based on our primary screening of antioxidant small molecule compounds library, a small molecule compound C2968 (chrysin) was identificated to expand cord blood CD34+ cells in vitro. Then we further verified the optimum concentration and explored its effect on hHSCs phenotype and biological function. C2968 could significantly increase the proportion and absolute number of CD34+CD38−CD49f+ and CD34+CD38−CD45RA−CD90+ cells under 2.5 μM. Furthermore, the total number of colony-forming units and the frequency of LT-HSCs in C2968-treated group were significantly higher than control, indicating the multipotency and long-term activity of hematopoietic stem and progenitor cells were sustained. Additionally, C2968 treatment could maintain transplantable HSCs that preserve balanced multilineage potential and promote rapid engraftment after transplantation in immunodeficient (NOG) mice. Mechanistically, the activity of chrysin might be mediated through multiple mechanisms namely delaying HSC differentiation, inhibiting ROS-activated apoptosis, and modulating of cyclin-dependent kinase inhibitors. Overall, chrysin showed good ex vivo expansion effect on hHSCs, which could maintain the self-renewal and multilineage differentiation potential of hHSCs. Through further research on its antioxidant mechanism, it may become a promising tool for further fundamental research and clinical umbilical cord blood transplantation of hHSCs.https://www.frontiersin.org/article/10.3389/fphar.2020.00399/fullantioxidantsmall molecule compoundchrysinex vivo expansionhematopoietic stem cellsself-renewal |
| spellingShingle | Yinghui Li Mei He Wenshan Zhang Ming Yang Yahui Ding Shiqi Xu Jiali Gu Yafang Li Jingjing Yin Yingdai Gao Antioxidant Small Molecule Compound Chrysin Promotes the Self-Renewal of Hematopoietic Stem Cells Frontiers in Pharmacology antioxidant small molecule compound chrysin ex vivo expansion hematopoietic stem cells self-renewal |
| title | Antioxidant Small Molecule Compound Chrysin Promotes the Self-Renewal of Hematopoietic Stem Cells |
| title_full | Antioxidant Small Molecule Compound Chrysin Promotes the Self-Renewal of Hematopoietic Stem Cells |
| title_fullStr | Antioxidant Small Molecule Compound Chrysin Promotes the Self-Renewal of Hematopoietic Stem Cells |
| title_full_unstemmed | Antioxidant Small Molecule Compound Chrysin Promotes the Self-Renewal of Hematopoietic Stem Cells |
| title_short | Antioxidant Small Molecule Compound Chrysin Promotes the Self-Renewal of Hematopoietic Stem Cells |
| title_sort | antioxidant small molecule compound chrysin promotes the self renewal of hematopoietic stem cells |
| topic | antioxidant small molecule compound chrysin ex vivo expansion hematopoietic stem cells self-renewal |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00399/full |
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